Pregabalin Viatris (Previously Pregabalin Mylan)

Summary of the safety profile The pregabalin clinical programme involved over 8900 patients exposed to pregabalin, of whom over 5600 were in double-blind placebo controlled trials. The most commonly reported adverse reactions were dizziness and somnolence.

Adverse reactions were usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence.

Tabulated list of adverse reactions In table 2 below all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient, are listed by class and frequency (very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data)).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The adverse reactions listed may also be associated with the underlying disease and/or concomitant medicinal products. 4). Additional reactions reported from post-marketing experience are included in italics in the list below.

Table 2. Pregabalin Adverse Drug Reactions System Organ Class Adverse drug reactions Infections and infestations Common Nasopharyngitis Blood and lymphatic system disorders Uncommon Neutropaenia Immune system disorders Uncommon Rare Hypersensitivity Angioedema, allergic reaction Metabolism and nutrition disorders Common Uncommon Appetite increased Anorexia, hypoglycaemia Psychiatric disorders Common Uncommon Rare Not known Euphoric mood, confusion, irritability, disorientation, insomnia, libido decreased Hallucination, panic attack, restlessness, agitation, depression, depressed mood, elevated mood, aggression, mood swings, depersonalisation, word finding difficulty, abnormal dreams, libido increased, anorgasmia, apathy Disinhibition, suicidal behaviour, suicidal ideation Drug dependence Nervous system disorders Very common Common Uncommon Dizziness, somnolence, headache Ataxia, coordination abnormal, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy Syncope, stupor, myoclonus, loss of consciousness, psychomotor hyperactivity, dyskinesia, dizziness postural, intention tremor, nystagmus, cognitive disorder, mental impairment, speech disorder, hyporeflexia, Rare hyperaesthesia, burning sensation, ageusia, malaise Convulsion, parosmia, hypokinesia, dysgraphia, parkinsonism Eye disorders Common Uncommon Rare Vision blurred, diplopia Peripheral vision loss, visual disturbance, eye swelling, visual field defect, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, lacrimation increased, eye irritation Vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, visual brightness Ear and labyrinth disorders Common Uncommon Vertigo Hyperacusis Cardiac disorders Uncommon Rare Tachycardia, atrioventricular block first degree, sinus bradycardia, congestive heart failure QT prolongation, sinus tachycardia, sinus arrhythmia Vascular disorders Uncommon Hypotension, hypertension, hot flushes, flushing, peripheral coldness Respiratory, thoracic and mediastinal disorders Uncommon Rare Not known Dyspnoea, epistaxis, cough, nasal congestion, rhinitis, snoring, nasal dryness Pulmonary oedema, throat tightness Respiratory depression Gastrointestinal disorders Common Uncommon Vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth Gastrooesophageal reflux disease, salivary hypersecretion, hypoaesthesia oral Rare Ascites, pancreatitis, Swollen tongue, dysphagia Hepatobiliary disorders Uncommon Rare Very rare Elevated liver enzymes* Jaundice Hepatic failure, hepatitis Skin and subcutaneous tissue disorders Uncommon Rare Rash papular, urticaria, hyperhidrosis, pruritus Stevens Johnson syndrome, Toxic Epidermal Necrolysis, cold sweat Musculoskeletal and connective tissue disorders Common Uncommon Rare Muscle cramp, arthralgia, back pain, pain in limb, cervical spasm Joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness Rhabdomyolysis Renal and urinary disorders Uncommon Rare Urinary incontinence, dysuria Renal failure, oliguria, urinary retention Reproductive system and breast disorders Common Uncommon Rare Erectile dysfunction Sexual dysfunction, ejaculation delayed, dysmenorrhoea, breast pain Amenorrhoea, breast discharge, breast enlargement, gynaecomastia General disorders and administration site conditions Common Uncommon Oedema peripheral, oedema, gait abnormal, fall, feeling drunk, feeling abnormal, fatigue Generalised oedema, face oedema, chest tightness, pain, pyrexia, thirst, chills, asthenia Investigations Common Weight increased Uncommon Rare Blood creatine phosphokinase increased, blood glucose increased, platelet count decreased, blood creatinine increased, blood potassium decreased, weight decreased White blood cell count decreased * Alanine aminotransferase increased (ALT) and aspartate aminotransferase increased (AST).

After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed. The following symptoms have been reported: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, suicidal ideation, pain, hyperhidrosis and dizziness.

These symptoms may indicate drug dependence. The patient should be informed about this at the start of the treatment. Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence […]

Skin reactions Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment.

At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, pregabalin should be withdrawn immediately and an alternative treatment considered (as appropriate).

Diabetic patients In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medicinal products. Hypersensitivity reactions There have been reports in the post-marketing experience of hypersensitivity reactions, including cases of angioedema.

Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Dizziness, somnolence, loss of consciousness, confusion and mental impairment Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population.

There have also been post-marketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product.

Vision-related effects In controlled trials, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. 1). In the post-marketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient.

Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms. Renal failure Cases of renal failure have been reported and in some cases discontinuation of pregabalin did show reversibility of this adverse reaction.

Withdrawal of concomitant anti-epileptic medicinal products There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy on pregabalin.

Congestive heart failure There have been post-marketing reports of congestive heart failure in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication.

Pregabalin should be used with caution in these patients. Discontinuation of pregabalin may resolve the reaction. Treatment of central neuropathic pain due to spinal cord injury In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased.

g. anti-spasticity agents) needed for this condition. This should be considered when prescribing pregabalin in this condition. Respiratory depression There have been reports of severe respiratory depression in relation to pregabalin use.

Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly may be at higher risk of experiencing this severe adverse reaction. 2). Suicidal ideation and behaviour Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications.

A meta-analysis of randomised placebo controlled studies of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known. 8). An epidemiological study using a self controlled study design (comparing treatment periods with non-treatment periods within an individual) showed evidence of an increased risk of new onset of suicidal behaviour and death by suicide in patients treated with pregabalin.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered.

Discontinuation of pregabalin treatment should be considered in case of suicidal ideation and behaviour. g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics.

When pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly). 5). 36]). This […]

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